Using novel virtual reality tasks to identify neural mechanisms of discrimination learning in PTSD

创伤后应激障碍（PTSD）是一种高度流行和衰弱的疾病。尽管 尽管我们努力描述PTSD的病理生理学特征，但还没有建立生物标志物来帮助 诊断、治疗开发和治疗反应预测。新的证据表明 创伤后应激障碍是通过对威胁和奖励中的环境/线索的功能失调的辨别来介导的， 处理，涉及海马体，杏仁核，和前额皮质。 尽管如此，上下文的组成部分，或形成的心理边界的环境（心理 表示），其在单个表示内描绘威胁/安全和奖励/非奖励提示/信号。 环境，这些过程的神经回路尚未在PTSD中进行研究， 上下文处理常常受损。 我已经开发了两个虚拟现实（VR）任务来检查威胁和奖励歧视， 评估在一个环境中学习效价歧视的潜在机制， 位置特定信息。简而言之，用于本研究的任务由中性（CS-）和 威胁或奖励（CS+）区域，在一个单一的环境中，参与者必须使用空间 学习如何区分这两个领域。这项任务旨在揭示大脑 参与学习位置预测环境奖励的区域。 这项研究计划旨在调查PTSD患者之间的大脑活动差异 （n=80）、无PTSD的创伤暴露对照（TE; n=80）和健康对照（HC; n=80）。 在VR范例中的功能性磁共振成像（fMRI）将用于阐明 威胁和奖励学习以及辨别处理的神经机制 组多个级别的评估将包括多模式MRI，加上外周 唤醒的测量（例如，皮肤电导率响应）、眼动跟踪和 学习 这是阐明威胁和奖励辨别学习过程的第一步， 环境，特别是为了阐明神经信号是否特异于价信号或 创伤后应激障碍的精神病理学从长远来看，这项研究将揭示具体的 在一个环境中，辨别学习所需的大脑区域的作用， 开发有效的诊断和治疗PTSD和其他精神病理学。

Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating disorder. Despite efforts to characterize PTSD pathophysiology, no biomarkers have been established to aid in diagnosis, treatment development, and prediction of treatment response. New evidence poses that PTSD is mediated by dysfunctional discrimination of context/cues in both threat and reward processing, involving the hippocampus, nucleus accumbens, amygdala, and prefrontal cortex. Still, the contextual component, or the formation of mental boundaries of the environment (mental representations) that delineate threat/safety and reward/non-reward cues/signals within a single environment, and the neural circuits of these processes are yet to be studied in PTSD where contextual processing is often impaired. I have developed two virtual reality (VR) tasks to examine threat and reward discrimination, to assess the underlying mechanisms of learning valence discrimination within an environment using location-specific information. Briefly, the task used for this study consists of neutral (CS-) and threat or reward (CS+) areas, within a single environment, and participants must use spatial information to learn to discriminate between both areas. The task is designed to reveal brain regions involved in learning locations predictive of environmental reward. This research proposal aims to investigate brain activity differences between patients with PTSD (n=80), trauma-exposed controls without PTSD (TE; n=80), and healthy controls (HC; n=80). Functional magnetic resonance imaging (fMRI) during the VR paradigm will be used to clarify the neural mechanisms underlying threat and reward learning and discrimination processing across groups. Multiple levels of assessment will include multimodal MRI, coupled with peripheral measures of arousal (e.g., Skin Conductance Response), eye-tracking, and subjective ratings of learning. This is a first step to clarify the process of threat and reward discrimination learning within an environment, particularly to elucidate if the neural signatures are specific to valence signaling or to PTSD psychopathology in general. In the long term, this research will shed light on the specific role of brain areas needed for discrimination learning within an environment which will advance the development of effective diagnostics and treatments for PTSD and other psychopathologies.